Lancefield group B streptococci (GBS) are a major cause of neonatal sepsis (Baker et al. (1990) Rev. Infect. Dis. 12(Suppl. 4):S463-8) and are important pathogens in adults (Farley (2001) Clin. Infect. Dis. 33(4):556-61). There are two main divisions of neonatal GBS disease, early- and late-onset disease (Baker et al. (1990) supra; Ferrieri (1985) Antibiot. Chemother. 35:211-24) Early-onset disease occurs within the first week of life and is vertically transmitted from mother to infant, with eighty percent of all GBS infections being of this type. All of the known serotypes have been isolated from infants suffering from early-onset disease. Three manifestations of early-onset disease include sepsis with no known focus of infection, meningitis, and pneumonia. Late-onset disease occurs from one week to three months after birth. Serotype III GBS are responsible for approximately 90% of all late-onset infections (Baker et al. (1990) supra), with meningitis being a common clinical manifestation that results in a substantial number of survivors suffering permanent neurological damage. Serotype III organisms are responsible for approximately 90% of all cases of meningitis (Baker et al. (1990) supra), whether or not the meningitis is a result of early- or late-onset disease. Therefore, serotype III GBS are responsible for a substantial portion of GBS disease.
Several surface proteins from group B streptococci have been identified in an attempt to characterize the complex nature of the cell wall and polysaccharide capsule. C-protein was first described using a polyclonal rabbit antiserum made against whole formalin-killed cells of CDC strain A909 (Wilkinson and Eagon (1971) Infect. Immun. 4(5):596-604). Antibodies against group- and serotype-specific carbohydrates in polyclonal rabbit antiserum were eliminated by exhaustive adsorption with a c-protein-negative serotype Ia strain, and the non-serotype Ia antigens that the antiserum bound to were called the c-protein. It was later recognized that c-protein typing serum actually recognizes at least four antigenic moieties, alpha, beta, (Wilkinson and Eagon (1971) supra; Johnson and Ferrieri (1984) J. Clin. Microbiol. 19(4):506-10; Bevanger (1985) Acta. Pathol. Microbiol. Immunol. Scand. [B] 93(2):113-9) gamma, and delta (Brady et al. (1988) J. Infect. Dis. 158(5):965-72; Chun et al. (1991) J. Infect. Dis. 163(4):786-91). The genes encoding the alpha and beta proteins have been cloned (Cleat and Timmis (1987) Infect. Immun. 55(5):1151-5; Michel et al. (1991) Infect. Immun. 59(6):2023-8) and the encoded proteins characterized. Reactivity of gamma has been found to correspond to a variant amino-terminus of the alpha protein. The nature of the epsilon antigen is unclear, although it is associated with acyl-carrier protein in cell sonicates and SDS extracts of GBS whole cells (Seifert, et al. (2003) Gen. Meet. Am. Soc. Microbiol. 103rd, Washington, D.C.). Another antigenic marker, protein Rib (resistance to protease, immunity, group B), which is immunologically distinct from delta, has also been described (Stalhammar-Carlemalm et al. (1993) J. Exp. Med. 177(6):1593-603). The alpha, beta, and gamma antigens are expressed primarily by serotype Ia, Ib, and II organisms, while delta and Rib have been reported to be expressed by most serotype III strains (Brady et al. (1988) supra; Chun et al. (1991) supra; Stalhammar-Carlemalm et al. (1993) supra). Other surface proteins that have been identified include the R and X proteins (Ferrieri (1988) Rev. Infect. Dis. 10(Suppl 2):S363-6), C5a peptidase (Beckmann et al. (2002) Infect. Immun. 70(6):2869-76; Cleary et al. (1992) Infect. Immun. 60(12):5219-23), Sip (Brodeur et al. (2000) Infect. Immun. 68(10):5610-8), Lmb (Spellerberg et al. (1999) Infect. Immun. 67(2):871-8), Fbs, and a Rib-like protein (Areschoug et al. (1999) Infect. Immun. 67(12):6350-7). Collectively, these studies indicate that a variety of molecules, several of unknown function, are present on the surface of GBS and some of these are more commonly detected on strains within a given serotype.
In addition to classifying GBS according to polysaccharide capsule, serotype III GBS isolates can be further classified based on HindIII and Sse83871 restriction digest patterns (RDPs) of chromosomal DNA into four distinct lineages, designated RDP types III-1, -2, -3, and -4 (Takahashi et al. (1998) J. Infect. Dis. 177(4):1116-9). The majority (91%) of serotype III invasive neonatal isolates have been reported to be RDP III-3, suggesting that these strains may represent a more virulent lineage of serotype III GBS. Genomic subtractive hybridization has been used to identify DNA sequences unique to RDP III-3 strains (e.g., clones AA3.8, AA3.14, AA3.16, AA4.1, AA4.13, AW-10, DY-1, DY-3, and DY-11) (Bohnsack et al. (2002) Infect. Immun. 70(1):134-9), however, individual coding sequences within most of these clones have not been identified and characterized as to their contribution to the pathogenicity of RDP III-3 GBS.